Neoadjuvant Dasatinib Plus LHRH Analogue Therapy in High-Risk Localized Prostate Cancer

A Phase II Study of Neoadjuvant Dasatinib Plus LHRH Analogue Therapy in High-Risk Localized Prostate Cancer

This trial will investigate the activity of dasatinib plus LHRH analogue therapy in high-risk localized prostate cancer.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Dasatinib; Drug: Leuprolide Acetate (LHRH Analogue); Procedure: Radical Prostatectomy

Detailed Description

OUTLINE: This is a multi-center study.

• Dasatinib -100 mg administered once daily per oral route for 28 consecutive days.
• Leuprolide acetate - 7.5 mg administered subcutaneously on day 1 every 28 days (+ 7 days).

The 28 days of dasatinib and leuprolide injection (plus the time required to recover from toxicity if encountered) is defined as a cycle. Patients will be treated for up to a maximum of 3 cycles of dasatinib and leuprolide acetate.

Radical Prostatectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Hematopoietic:

• Hemoglobin (Hgb) ≥ 8.0 g/dL
• Platelets ≥ 100 K/mm3
• Absolute neutrophil count (ANC) ≥ 1.0 K/mm3

Hepatic:

• Total bilirubin < 2.0 X Upper Limit Normal (ULN)
• Aspartate aminotransferase (AST) < 2.5 X ULN
• Alanine aminotransferase (ALT) < 2.5 X ULN

Renal:

• Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula

Cardiovascular:

• No uncontrolled angina, congestive heart failure or myocardial infarction within 6 months prior to registration for protocol therapy.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Galesburg, Illinois, United States, 61401
      • Medical & Surgical Specialists, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate.
• Clinical stage T1-T3a disease.
• Must be willing to have a tumor biopsy, if previous tumor tissue unavailable for tumor marker analysis.
• Kattan pre-operative nomogram-predicted (based on stage, Prostate Specific Antigen (PSA) and Gleason score) 5-year risk of recurrence-free survival of 80% or less
• Must be deemed eligible for radical prostatectomy.
• Must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.
• Written informed consent and HIPAA authorization for release of personal health information.
• Age > 18 years at the time of consent.

Exclusion Criteria:

• No evidence of regional, lymph node or distant metastasis on clinical or radiological assessments. All baseline radiology studies must be performed within 28 days prior to registration for protocol therapy.
• No prior malignancy in the past 2 years except for basal cell and squamous cell carcinoma of the skin. Other cancers with low potential for metastasis, such as in situ cancers (e.g., Grade 1, TA TCC (low grade superficial bladder cancer), and colonic polyp with focus of adenocarcinoma) can be enrolled after approval from the Sponsor Investigator.
• No prior hormonal therapy with the exception of oral 5-alpha-reductase inhibitors (finasteride, dutasteride, etc.). Patients who have received prior oral anti-androgen therapies (bicalutamide, flutamide, nilutamide, etc.), prior LHRH agonist therapy (leuprolide, goserelin acetate, etc.), or prior orchiectomy are ineligible.
• No prior systemic chemotherapy or radiotherapy for prostate cancer is allowed. Transurethral resection of the prostate for benign prostatic hypertrophy (BPH) and oral alpha-blockers (terazosin, tamsulosin, doxazosin) are permitted.
• No history of hemorrhage or thrombotic events (cerebrovascular accident, deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to registration for protocol therapy.
• No history of diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
• No history of diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) of registration on protocol therapy.
• No history of ongoing or recent (≤ 3 months of registration on protocol therapy) significant gastrointestinal bleeding
• No ongoing anti-coagulation and/or anti-platelet therapies allowed.
• No unresolved pleural or pericardial effusion of any grade within 3 months of registration for protocol therapy.
• No uncontrolled angina, congestive heart failure or MI within 6 months prior to registration for protocol therapy.
• No diagnosed congenital long QT syndrome.
• No history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).
• No prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
• Following medications must be discontinued at least 7 days prior to registration for protocol therapy and be withheld for the duration of dasatinib therapy:
• Drugs that are generally accepted to have a risk of causing Torsades de Pointes
• Patient must not be receiving any prohibited CYP3A4 inhibitors /inducers/ substrates
• Anti-coagulation and/or anti-platelet therapies - to avoid potential bleeding risks.
• No major surgical procedure, open biopsy, or significant trauma within 28 days prior to registration for protocol therapy.
• Ability to comply with study and/or follow-up procedures and requirements.
• No treatment with any investigational agent for any medical condition within 28 days prior to registration for protocol therapy.
• No clinically significant infections or any other condition which, in the investigator's opinion, deems the patient an unsuitable candidate to receive the study drug.
• Ability to take oral medication (dasatinib must be swallowed whole).
• No known history of hypokalemia that cannot be corrected prior to registration on protocol therapy.
• No known history of hypomagnesemia that cannot be corrected prior to registration on protocol therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm Assignment; Neoadjuvant dasatinib plus leuprolide acetate followed by radical prostatectomy

Drug: Dasatinib; Dasatinib 100 mg administered once daily per oral route for 28 consecutive days; Drug: Leuprolide Acetate (LHRH Analogue); Leuprolide acetate 7.5 mg administered subcutaneously on day 1 every 28 days (+ 7 days).; Procedure: Radical Prostatectomy; Radical prostatectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered dasatinib dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To Estimate the Pathologic Complete Response (pCR) Rate	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To Estimate Partial Pathologic Responses (pPR)	18 months
To Estimate PSA Response Rate	18 months
To Estimate Progression Free Survival	18 months
To Evaluate the Impact of Dasatinib Plus LHRH on Expression of Selected Biomarkers	18 months
To Estimate Safety and Tolerability of LHRH Plus Dasatinib	18 months

Collaborators and Investigators

• Sponsor: Noah Hahn, M.D.
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• Hoosier Oncology Group Homepage

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: March 11, 2009
• First Submitted That Met QC Criteria: March 11, 2009
• First Posted (Estimate): March 12, 2009

Study Record Updates

• Last Update Posted (Actual): March 14, 2018
• Last Update Submitted That Met QC Criteria: February 14, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide; Dasatinib
• Other Study ID Numbers: HOG GU07-124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO